Contactin associates with Na+ channels and increases their functional expression

Contactin (also known as F3, F11) is a surface glycoprotein that has signif icant homology with the beta2 subunit of voltage-gated Na+ channels. Contac tin and Na+ channels can be reciprocally coimmunoprecipitated from brain ho mogenates, indicating association within a complex. Cells cotransfected wit h Na+ channel Na(v)1.2 alpha and beta1 subunits and contactin have threefol d to fourfold higher peak Na+ currents than cells with Na(v)1.2 alpha alone , Na(v)1.2/beta1, Na(v)1.2/contactin, or Na(v)1.2/beta1/beta2. These cells also have a correspondingly higher saxitoxin binding, suggesting an increas ed Na+ channel surface membrane density. Coimmunoprecipitation of different subunits from cell lines shows that contactin interacts specifically with the beta1 subunit. In the PNS, immunocytochemical studies show a transient colocalization of contactin and Na+ channels at new nodes of Ranvier formin g during remyelination. In the CNS, there is a particularly high level of c olocalization of Na+ channels and contactin at nodes both during developmen t and in the adult. Contactin may thus significantly influence the function al expression and distribution of Na+ channels in neurons.